Synthesis and Structure-Activity Relationships of Imidazopyridine/Pyrimidine- and Furopyridine-Based Anti-infective Agents against Trypanosomiases

Autor(es):Mostrar menos -

Silva, Daniel G. ^{[1, 2]} ; Junker, Anna ^[2] ; de Melo, Shaiani M. G. ^[1] ; Fumagalli, Fernando ^[3] ; Gillespie, J. Robert ^[4] ; Molasky, Nora ^[4] ; Buckner, Frederick S. ^[4] ; Matheeussen, An ^[5] ; Caljon, Guy ^[5] ; Maes, Louis ^[5] ; Emery, Flavio S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, QHeteM Lab Quim Heterocicl & Med, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Westphalian Wilhelms Univ, European Inst Mol Imaging EIMI, D-48149 Munster - Germany

^[3] Univ Fed Santa Maria UFSM, Ctr Ciencias Saude CCS, Av Roraima 1000, BR-97105900 Santa Maria, RS - Brazil

^[4] Univ Washington, Dept Med, Seattle, WA 98195 - USA

^[5] Univ Antwerp, Lab Microbiol Parasitol & Hyg LMPH, Univ Pl 1, B-2610 Antwerp - Belgium

• Tipo de documento: Artigo Científico
• Fonte: CHEMMEDCHEM; v. 16, n. 6 NOV 2020.
• Citações Web of Science: 0

Resumo

Neglected tropical diseases remain among the most critical public health concerns in Africa and South America. The drug treatments for these diseases are limited, which invariably leads to fatal cases. Hence, there is an urgent need for new antitrypanosomal drugs. To address this issue, a large number of diverse heterocyclic compounds were prepared. Straightforward synthetic approaches tolerated pre-functionalized structures, giving rise to a structurally diverse set of analogs. We report on a set of 57 heterocyclic compounds with selective activity potential against kinetoplastid parasites. In general, 29 and 19 compounds of the total set could be defined as active against Trypanosoma cruzi and T. brucei brucei, respectively (antitrypanosomal activities <10 mu M). The present work discusses the structure-activity relationships of new fused-ring scaffolds based on imidazopyridine/pyrimidine and furopyridine cores. This library of compounds shows significant potential for anti-trypanosomiases drug discovery. (AU)

• Processo FAPESP: 17/21146-4 - Explorando a química heterocíclica e a epigenética para o desenvolvimento de compostos de interesse químico medicinal
• Beneficiário: Flavio da Silva Emery
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/22001-0 - Síntese e avaliação de novos compostos heterociclos como potenciais agentes tripanossomicidas
• Beneficiário: Daniel Gedder Silva
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado